The major objectives of this proposal are to investigate the kinetics of striatal dopamne metabolism bilaterally and determine the changes induced after the acute and chronic administration of haloperidol--a potent D2 receptor blocking antipsychotic. To accomplish this, the increase of dopamine and the decline of its acidic metabolites, DOPAC and HVA, over time after inhibition of monoamine oxidase will be quantitated by gas-liquid (electron capture) chromatography in normal surgically unaltered rats previously tested for spontaneous rotation during the dark phase of their diurnal cycle. Fractional rate constants and turnover rates will be determined and compared in two ways: left versus right striatum, and the striatum, and the ipsilateral striatum versus the one contralateral to the dominant direction of spontaneous nocturnal rotation. These studies may indicate, as preliminary data suggests, that turnover is significantly greater in the striatum ipsilateral to the dominant direction of rotation for drug-free rats, but greater in the opposite (contralateral) striatum for those receiving haloperidol. Perhaps neuroleptics work similarly in man. By daapening excess dopaminergic activity in the dominant hemisphre (e.g. striatum) or increasing the activity of the other, neuroleptics may restore a normal balance, or imbalance, between the two halves of the brain. To assure that the bilateral asymmetrical effect of haloperidol is not simply due to an unequal bilateral cerebral distribution, concentrations of the drug will be determined in each striatum. Moreover in order to evaluate the relative contribution of each striatum to the normal and h aloperidol-induced bilateral differences in dopamine metabolism, acidic metabolites will be determined in haloperidol-treated and control rats after a section of the anterior corpus callosum. These data may indicate that the two striata function relatively indepentently of one another or, on the contrary, that one striatum modulates or even directs the neurochemical changes of the other.